Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE180268 | GEO | 2021/07/20
REPOSITORIES: GEO
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Project description:Introduction: Human Papilloma Virus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC), between 15% and 35% of HNSCC harboring HPV, almost exclusively of subtype 16. Demographic and exposure differences between HPV-positive (+) and negative (-) HNSCCs suggest that HPV(+) tumors may constitute a subclass with different biology, while clinical differences have also been observed. In this study, gene expression profiles of HPV(+) and (-) tumors were compared to further explore the biological effect of HPV in HNSCC. Methods: Thirty-six HNSCC tumors were analyzed for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV using consensus primers for HPV L1, E6 and E7 by PCR and RT-PCR. Results: Eight (22%) of 36 tumors were positive for HPV, all of the HPV 16 subtype, and the HPV positive samples also expressed viral HPV E6 mRNA determined by RT-PCR. Patients with HPV(+) HNSCCs were on average younger than those with HPV(-) tumors (mean age 50.2 vs. 58.7). Statistical analysis using Significance Analysis of Microarrays (SAM) based on HPV status as a supervising parameter resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a sub-set of these genes were verified by RT-PCR. Genes highly expressed in HPV(+) samples included cell cycle regulators (p16INK4A, p18 and CDK2) and transcription factors (TAF7L, RFC4, RPA2 and TFDP2). The microarray data were also investigated using DIGMap to map genes by chromosomal location. A large number of genes on chromosome 3q24-qter was found to be overrepresented in HPV(+) tumors. Conclusion: The gene expression profile associated with HPV reflects alterations in cell cycle and proliferation signals. Further investigation of differentially expressed genes may reveal the unique pathways in HPV(+) tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment. Keywords: HPV, HNSCC, head and neck cancer, human, human papilloma virus
2005-11-28 | GSE3292 | GEO
Project description:We report the first RNA-Seq experiments profiling the effects of DEK loss in HNSCC. Our data also incorporates HPV+ and HPV- tumors to idenfity HPV-dependent and -independent gene signatures.
2016-02-05 | GSE70462 | GEO
Project description:Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs), 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC. Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells. Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. Keywords: Gene expression ptofiles of primary cancers
2007-05-15 | GSE6791 | GEO
Project description:We report the first RNA-Seq experiments profiling the effects of DEK loss in HNSCC. Our data also incorporates HPV+ and HPV- tumors to idenfity HPV-dependent and -independent gene signatures. RNA-Seq of DEK-dependent gene signatures in HNSCC cell lines
2016-02-05 | E-GEOD-70462 | biostudies-arrayexpress
Project description:To identify HPV interaction region, two cell lines (UPCI-SCC-090, UM-SCC-104) were subjected to 4C-seq analysis.
2023-01-06 | GSE211280 | GEO
Project description:Gene expression analysis of p63 knockdown in 2 HPV+ HNSCC cell lines using RNA-seq, Genomic profiling of p63 binding across 2 HPV+ HNSCC cell lines, Epigenomic landscape of 2 HPV+ HNSCC cell lines
2022-04-19 | GSE182133 | GEO
Project description:We report single cell transcriptome data from HPV-positive head and neck squamous cell carcinoma patients
2023-06-20 | GSE173468 | GEO
Project description:Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs), 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC. Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells. Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. Experiment Overall Design: All tissue samples were fresh frozen in liquid nitrogen and collected with patientsâ?? consent under approval of the Institutional Review Boards from all participating institutions. Each tissue sample was cryosectioned, and selected sections stained with hematoxylin/eosin, and reviewed to determine tumor content, pathological status, and freedom from necrosis and freezing artifacts. Epithelial cells from all normal samples and tumor cells from HNC or CC samples with less than 80% tumor were laser capture microdissected from adjacent sections using a PixCell II LCM system. For guidance, an adjacent section was briefly stained with hematoxylin to visualize tissue structure. Total RNA was extracted from sectioned and/or microdissected samples as follows: 1 ml of TRIzol (Invitrogen, Carlsbad, CA) was added to each tissue sample, homogenized by passing through a 20 gauge needle, and added to 0.2 ml chloroform. After centrifugation at 20,000 xg for 20 min at 4oC, RNA in the aqueous phase was precipitated with an equal volume of isopropanol for 30 min at 4oC, pelleted, and washed twice with cold 70% ethanol. Double strand (ds) cDNA was synthesized from this RNA using a SuperScript ds cDNA synthesis kit (Invitrogen) and T7 promoter-linked oligo (dT)24. Complementary RNA (cRNA) was synthesized from T7 promoter-linked ds cDNA using a MEGAscript high transcription kit (Ambion, Austin, TX). To obtain a sufficient cRNA for 2 microarray hybridizations, this amplification process was repeated. Second round cRNA was biotin labeled using a BioArray High Yield RNA Transcript Labeling Kit (Enzo Life Sciences, Farmingdale, NY) and stored at -80oC until hybridized. cRNA quality and quantity was determined by gel electrophoresis and UV spectrophotometry. Whole human gene expression was profiled using Affymetrix Human Genome U133 Plus 2.0 arrays.
2008-06-15 | E-GEOD-6791 | biostudies-arrayexpress
Project description:Background. Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers, for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described and the evidence of a functional impact on gene expression is still limited. Methods. We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours . Results. We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only 5 CpGs in few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA-Sequencing in the TCGA cohort. Conclusions. We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.
2017-02-18 | GSE95036 | GEO
Project description:Purpose: There is substantial heterogeneity within the human papillomavirus (HPV) positive head and neck cancer (HNC) tumors that predispose them to different outcomes, however this subgroup is poorly characterized due to various historical reasons. Experimental Design: we perform unsupervised gene expression clustering on well-annotated HPV(+) HNC samples from two cohorts ( 84 total primary tumors), as well as 18 HPV(-) HNCs, to discover subtypes, and begin to characterize the differences between the subtypes in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number variations and mutation frequencies. Results: We identified two distinctive HPV(+) subtypes by unsupervised clustering. Membership in the HPV(+) subtypes correlates with genic viral integration status, E2/E4/E5 expression levels and the ratio of spliced to full length HPV oncogene E6. The subtypes also show differences in copy number alterations, in particular the loss of chr16q and gain of chr3q, PIK3CA mutation, and in the expression of genes involved in several biological processes related to cancer, including immune response, oxidation-reduction process, and keratinocyte and mesenchymal differentiation. Conclusion: Our characterization of two subtypes of HPV(+) tumors provides valuable molecular level information in relation to the alternative paths to tumor development and to that of HPV(-) HNCs. Together, these results will shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients.
2016-05-13 | GSE74949 | GEO